Abstract 2050
Background
Elevated LDH is a known predictive and prognostic factor correlating with poor response rates and survival in patients (pts) with metastatic melanoma (MM) treated with targeted therapy (BRAF plus MEK inhibitors, TT) or immune checkpoint inhibitors (ICI). Whether TT or ICI in this subgroup of pts is more beneficial is unknown.
Methods
Pts with MM and elevated LDH who started first-line therapy between March 2016 and June 2017 were retrospectively identified from 25 melanoma centers. The cohort was divided into 2 groups: pts receiving TT first-line (TT group) and ICI first-line (ICI group). Primary endpoints were overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Demographics and disease characteristics were also examined.
Results
404 pts with elevated LDH at start of first-line systemic treatment (ST) received either TT (n = 90, 22%) or ICI (n = 314, 78%). TT included dabrafenib and trametinib (73%) and vemurafenib and cobimetinib (27%). ICI included pembrolizumab (47%), nivolumab (11%) and combination ipilimumab and nivolumab (40%). Median (med) follow-up time was 11.2 months (mo). Med age was 65 years, 58% male, ECOG ≥1 46%, AJCC stage M1c 45%, M1d 31%, >3 organ sites 57%, BRAF-mutant 43%. 71% had LDH 1-2x upper limit normal (ULN), 27% >2x ULN. Age, sex, ECOG and AJCC stage were similar in both groups. All TT pts had BRAF mutant MM, compared to 32% with ICI. Pts in the TT group were more likely to have >3 organ sites involved (71% vs 54%, p = 0.003) or LDH >2x ULN (34% vs 24%, p = 0.15) compared to ICI group. The TT group had superior ORR (63% vs 36%, p ≤ 0.001) and PFS (med 4.7 mo vs 2.3 mo, p < 0.001), with similar OS (med 10.9 mo vs 17.9 mo, p = 0.7) than the ICI group. 56% of the pts in the TT group and 39% of the pts in the ICI group received a subsequent ST. ORR, PFS and OS for the BRAF-mutant subgroup comparing first-line ICI vs. TT will be presented.
Conclusions
In MM pts with elevated LDH at start of first-line ST, TT was associated with a higher ORR and longer med PFS. OS was similar in both groups, with patients undergoing ICI showing slightly longer med OS, however both groups did poorly. Clinical trials investigating the sequence of first-line therapies in pts with high medical need are urgently needed.
Clinical trial identification
Editorial acknowledgement
Kai-Martin Thoms, Göttingen; Simone Goldinger, Zurich; Friedegund Meier, Dresden; Carola Berking, Munich; Raphael Reinhard, Mannheim; Laura Susok, Bochum; Paolo Ascierto, Naples; Konstantin Drexler, Regensburg; Claudia Pföhler, Homburg; Julia Tietze, Augsburg; Alvaro Moreira, Erlangen.
Legal entity responsible for the study
University Clinic Essen, Department of Dermatology.
Funding
Has not received any funding.
Disclosure
S. Knispel: Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses: Novartis. M. Gassenmaier: Advisory / Consultancy, Research grant / Funding (self): Novartis. A.M. Menzies: Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche; Advisory / Consultancy: Pierre Fabre. C. Loquai: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Sun pharma; Advisory / Consultancy, Travel / Accommodation / Expenses: Biontech; Advisory / Consultancy, Travel / Accommodation / Expenses: Almirall. D.B. Johnson: Advisory / Consultancy: Array Biopharma; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): BMS; Advisory / Consultancy, Licensing / Royalties: Genoptix; Advisory / Consultancy, Research grant / Funding (self): Incyte; Advisory / Consultancy: Merck; Advisory / Consultancy: Novartis; Travel / Accommodation / Expenses: Genentech; Honoraria (institution): Pfizer; Honoraria (institution): Syndax; Honoraria (institution): Celldex; Honoraria (institution): Idera; Honoraria (institution): Merck; Honoraria (institution): Amgen; Honoraria (institution): Novartis; Honoraria (institution): Plexxikon. C. Franklin: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre. R. Gutzmer: Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Johnson & Johnson; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck-Serono; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Almirall-Hermal; Honoraria (self), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: SUN; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre; Advisory / Consultancy: LEO; Advisory / Consultancy: 4SC; Advisory / Consultancy: Incyte; Advisory / Consultancy: Takeda. J.C. Hassel: Honoraria (self), Research grant / Funding (institution): BMS; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self): Roche; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self), Advisory / Consultancy: Sanofi; Advisory / Consultancy: Pierre Fabre. C. Weishaupt: Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Pierre Fabre; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self): Curevac; Honoraria (self): Leo Pharma; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Takeda. T. Eigentler: Honoraria (self), Research grant / Funding (self): Roche; Honoraria (self), Research grant / Funding (self): MSD; Honoraria (self), Research grant / Funding (self): BMS; Honoraria (self): Pierre Fabre; Honoraria (self), Research grant / Funding (self): Novartis; Honoraria (self): Leo Pharma; Research grant / Funding (self): Curevac; Research grant / Funding (self): IOVANCE. F. Kiecker: Honoraria (self): Amgen; Honoraria (self): BMS; Honoraria (self): MSD; Honoraria (self), Research grant / Funding (self): Novartis; Honoraria (self): Roche; Honoraria (self): Pierre Fabre. C. Owen: Travel / Accommodation / Expenses: MSD. K.C. Kähler: Honoraria (self), Research grant / Funding (self): MSD; Honoraria (self): BMS; Honoraria (self): Novartis; Honoraria (self), Research grant / Funding (self): Philogen; Honoraria (self): Roche; Honoraria (self): Pierre Fabre. D. Niebel: Honoraria (self): BMS; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: BMS; Travel / Accommodation / Expenses: Celgene; Travel / Accommodation / Expenses: MSD. P. Mohr: Honoraria (self): Amgen; Honoraria (self), Research grant / Funding (self), Research grant / Funding (institution): BMS; Honoraria (self): GSK; Honoraria (self): Novartis; Honoraria (self), Research grant / Funding (self), Research grant / Funding (institution): MSD; Honoraria (self): Merck Serono; Honoraria (self): Pierre Fabre; Honoraria (self): Roche. D. Schadendorf: Honoraria (self), Honoraria (institution), Advisory / Consultancy: Pierre Fabre; Honoraria (self): Amgen; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Leo Pharma; Honoraria (self), Honoraria (institution): Roche; Honoraria (self): MSD; Honoraria (self): Incyte; Honoraria (self), Honoraria (institution): Regeneron; Honoraria (self): 4SC; Honoraria (self): AstraZeneca; Honoraria (self), Honoraria (institution), Research grant / Funding (self): BMS; Honoraria (self), Honoraria (institution): Merck-EMD; Honoraria (self): Pfizer; Honoraria (self), Honoraria (institution): Philogen; Honoraria (self): Array. L. Zimmer: Advisory / Consultancy: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre; Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD. All other authors have declared no conflicts of interest.
Resources from the same session
1984 - Induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma (NPC)
Presenter: Gizem Kaval
Session: Poster Display session 3
Resources:
Abstract
4822 - Efficiacy of different nutritional intervention on nutritional status and quality of life for local advanced nasopharyngeal carcinoma patients: a prospective clinical trial
Presenter: Yuan-yuan Chen
Session: Poster Display session 3
Resources:
Abstract
2628 - Apatinib in treating patients with platinum-resistant or platinum-refractory recurrent or metastatic nasopharyngeal carcinoma
Presenter: Changjuan Tao
Session: Poster Display session 3
Resources:
Abstract
4887 - Impact of tumor site and adjuvant radiotherapy on survival of adenoid cystic carcinoma: a SEER database analysis
Presenter: Jason Tasoulas
Session: Poster Display session 3
Resources:
Abstract
2634 - Efficacy and safety of anlotinib for patients with recurrent and/or metastatic salivary gland carcinomas
Presenter: Wen Jiang
Session: Poster Display session 3
Resources:
Abstract
3568 - ACCURACY a phase (P) 2 trial of AL101, a pan-Notch inhibitor, in recurrent/metastatic (R/M) adenoid cystic carcinoma (ACC) patients (pts) with Notch activating mutations (Notch act mut): preliminary safety and efficacy data.
Presenter: Renata Ferrarotto
Session: Poster Display session 3
Resources:
Abstract
683 - Pathologic Staging Changes in Oral Cavity Squamous Cell Carcinoma—Stage Migration and Implications for Adjuvant Treatment
Presenter: Zain Husain
Session: Poster Display session 3
Resources:
Abstract
563 - Expression of immune response biomarkers in head and neck squamous cell carcinoma (HNSCC) in irradiated area
Presenter: Carole Pflumio
Session: Poster Display session 3
Resources:
Abstract
4030 - HLA-Ligandome analysis reveals target antigens of oropharyngeal squamous cell carcinoma
Presenter: Simon Laban
Session: Poster Display session 3
Resources:
Abstract
2979 - Topographical distribution of sentinel lymph nodes in early tongue squamous cell carcinomas
Presenter: Hiroyuki Goda
Session: Poster Display session 3
Resources:
Abstract